The present proposal is directed towards an understanding of translational control mechanisms of hemoglobin synthesis particularly as they apply to human disease. The major objectives are to further define the requirements for optimal hemoglobin synthesis in intact and cell-free preparations of mammalian reticulocytes, as well as the effect of maturation on the cells' ability to effectively form polyribosomes (initiate globin chain synthesis). Studies will be directed towards identification and quantitation of hemin-dependent translational repressors in normal and iron-deficient human and rabbit erythrocytes. Experiments are designed to investigate whether iron in the form of heme is a universal requirement for initiation of protein synthesis in all mammalian cells. This proposal will also be directed towards an investigation of translational control in thalassemias. Furthermore, studies are being directed towards an understanding of the role of platelets in the pathophysiology of hemoglobinopathies.